Fabrication Of Multimodal Theranostics Based On Oxygen Vacancy Molybdenum Oxide And Anti-Tumor Applications

Photothermal therapy（PTT） and photodynamic therapy（PDT）have received extensive attention for their spatiotemporally controllable therapeutic effects.However,the PTT or PDT function of the near-infrared region or even visible light can often be realized,which shows a low utilization efficiency of the light source and severely limits the deep tumor treatment effect.Metal nanoparticles can bring rich and tunable band gaps through structural adjustment for their localized surface plasmon resonance（LSPR）,which effectively improve the utilization rate of light energy and are used in imaging and treatment.However,it is difficult to effectively achieve imaging and therapeutic effects for noble metals in NIR-Ⅱ.Also,noble metals are limited to clinical application for difficult biodegradation.Some oxygen-deficient metal oxides such as WO_x and Mo O_x have similar LSPR properties for the existence of oxygen vacancies.Tunable spectral absorption can be easily achieved by adjusting oxygen vacancies,thereby effectively achieving imaging and therapeutic effects in NIR-Ⅱ.Therefore,oxygen vacancies not only effectively realize the tunable absorption of laser,but also accelerates the recombination and separation rate of electron and holes by constructing a separation channel.Also,it realizes enhanced PTT and PDT in NIR-Ⅱ.The excellent properties brought by oxygen vacancy metal nanomaterials not only show good therapeutic performance in the phototherapy,but also show excellent therapeutic effect in sonodynamic therapy（SDT）.Oxygen vacancy metal nanomaterials construct electron-hole separation channels through oxygen vacancies,which can rapidly convert ultrasonic energy into separated electrons and holes,thereby achieving high efficiency SDT effects.Therefore,sonosensitizer nanoparticles based on oxygen vacancies have great potential in SDT and greatly compensate for the poor therapeutic effect of phototherapy for deep tumors.Therefore,the following researches are carried out based on oxygen vacancy metal nanoparticles in this paper:First,molybdenum oxide nanoparticles with full spectrum absorption were synthesized based on the localized surface plasmon resonance（LSPR）effect.Under the irradiation of 1064 nm laser,nanoparticles have strong photothermal conversion ability and electron energy transfer,so as to realize the PTT and PDT treatment process.At the same time,nanoparticles exhibit the catalytic effect of catalase,which can not only generate·OH for treatment through chemodynamic therapy（CDT）,but also catalyze the endogenous H₂O₂ of the tumor to generate O₂ to enhance the PDT effect and achieve PTT/PDT/CDT combination therapy effect in the NIR-Ⅱ.Oxygen vacancy-driven Gd³⁺has strong magnetic resonance signals and strong absorption of nanoparticles in NIR-Ⅱ,which can be used for magnetic resonance imaging（MRI）and photoacoustic imaging（PAI）of living organisms in NIR-Ⅱ.In addition,taking advantage of the delivery properties of nanoparticles in organisms and targeted modifications with charge flipping in response to the tumor microenvironment were designed.Secondly,partial reduction of Ti³⁺ is performed by template method to form Ti O₂/Mo O_3-xmicroporous nanoparticles with oxygen vacancies.On the one hand,Ti-based nanomaterials have strong spatial penetration characteristics in sonodynamic therapy,and have a good therapeutic effect on deep tumors.On the other hand,the regulation of oxygen vacancies and the design of the microporous structure build a fast separation channel for electrons and holes,which can speed up the energy transfer and conversion process in the process of SDT and CDT,thereby promoting the effect of SDT and CDT.Also,the microwells can be used to carry the chemotherapeutic drug doxorubicin（DOX）to achieve the effect of chemotherapy.Since ultrasound can improve the permeability of cell membranes and overcome tumor drug resistance,the combined treatment effect of SDT/CDT/CT can be achieved under ultrasound guidance.In addition,multivalent Mo ions undergo redox reactions with tumor endogenous substances such as H₂O₂,GSH responded to the tumor microenvironment.As a consequence,it can generate free radicals and release chemotherapy drugs that can be used for tumor cell therapy.Also,it has good degradation and metabolism properties.